Grant: Catalyst Grant: Invention and High-Risk, High-Benefit Research

Current methods for detection and treatment of a wide variety of diseases depend on isolation, selection, or evolution of molecular binding partners to a series of target molecules (proteins, DNA, small molecules) implicated in the disease state. Unfortunately, current methods for isolating such binding partners are slow, costly, and do not control for the specificity of the eventual binding reactions, only their affinities. We are developing a series of integrated microsystems comprised of label-free optical detection and monitoring methods, microfluidic technology including valves and pumps, all of which operate at tiny volumes. Such systems will be capable of selecting such molecular recognition reagents faster, cheaper, and with better specificity than is currently possible. Our work here is divided into two main research areas, microfluidic nucleic acid aptamer selection systems and microfluidic peptide selection systems. Both systems depend on surface plasmon resonance imaging, an optical technique used to measure the strength of binding between a target molecule and a ligand that binds to it. Our work focuses on the fabrication of arrays of such sensors within a microfluidic network, which makes each spot within the array individually addressable. Onto this base platform we then integrate heaters and temperature sensors for thermal cycling of these tiny volumes, which allows amplification of only the nucleic acids that are bound to the target molecules (aptamer selections), or we peel off the microfluidic polymer network and sequence bound peptides using mass spectrometry techniques (peptide selections). Such a technology will therefore allow selections of different classes of affinity reagents using a common system architecture. The use of microfluidics is essential to the success of these efforts, because the speed and precision of the binding reactions is controllable only in the small volumes generated using this technology.